Meta-analysis of amantadine efficacy for improving preclinical research reliability

While L-DOPA remines the gold standard symptomatic treatment for Parkinson’s disease (PD), its long-term use is often associated with motor fluctuations and dyskinesias. Currently, amantadine produces the most potent antidyskinetic effect in PD. However, side effects evoked by this drug limit its use, making treatment of L-DOPA-induced dyskinesia (LID) an open challenge. Preclinical models of PD are used to evaluate novel agents for LID in the MPTP-treated macaque monkeys, repeatedly exposed to L-DOPA. Like in PD patients, amantadine shows also antidyskinetic effects in this model.
In this paper, the authors investigated the magnitude of the antidyskinetic effect of amantadine and the reproducibility of its effect in MPTP-treated macaque monkeys by performing a meta-analysis consisting of 11 studies (using the exact same methodology in each case). The study showed that, although amantadine attenuated LID in MPTP-treated macaques, the magnitude of its response displayed great variability between studies. Thus, amantadine as a positive control should be tested along with potential antidyskinetic compounds in MPTP-treated macaques. The result of this meta-analysis also provides a basis for statistical power calculations for future studies assessing new antidyskinetic compounds on LID in the MPTP-treated macaques model. On a more general note, for routine and/or commonly used methods, thorough review of the literature and prior experiments (e.g. using meta-analysis tools) is essential for designing the most meaningful studies.